Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 6, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2005191118
Keywords
mRNA nanovaccine; TLR4; self-adjuvant; cancer immunotherapy; lipid-like material
Categories
Funding
- National Key R&D Program of China [2017YFC0908500/2017YFC0908503]
- National Natural Science Foundation of China [81773051, 81803005, 51973243]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S638]
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX10301402]
Ask authors/readers for more resources
The C1 lipid nanoparticle-based mRNA cancer nanovaccine efficiently delivers mRNA to antigen presenting cells, activates TLR4, induces inflammatory cytokines in dendritic cells, and shows significant antitumor efficacy.
Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available